Project Summary/Abstract Despite the overwhelming popularity of novel, high-tech, nicotine salt electronic cigarettes (ECs) such as JUUL as a harm reduction approach, basic knowledge about the abuse potential of these devices has not been characterized. The long-term goal is to describe the abuse potential of ECs to develop improved public health strategies to minimize tobacco product harm. The overall objective of this study is to use physiological, psychological, and behavioral laboratory assessments to identify EC device characteristics associated with positive perception and preference using high-tech nicotine salt ECs. Our central hypothesis is that key device characteristics such as nicotine delivery and flavor relate to young adult perception of ECs and preference in using them. The rationale of this study is that new evidence on the physiological and psychological basis of EC use?particularly with popular high-tech nicotine salt ECs currently dominating the market?will contribute to evidence for use by regulatory agencies such as the FDA in their quest to regulate ECs. The central hypothesis will be tested by pursuing three aims: 1) Characterize the basic pharmacokinetics of the popular EC, JUUL, with different flavor and nicotine strength options; 2) Evaluate the effects of nicotine delivery and flavor on subjective measures of JUUL abuse potential; and 3) Evaluate the effects of nicotine delivery and flavor on behavioral measures of JUUL abuse potential. Under the first aim, plasma nicotine pharmacokinetics will be measured and compared following JUUL EC use at either 3% or 5% nicotine salt by volume and either tobacco or mint flavor with an additional usual-brand-cigarette session. For the second aim, subjective responses to each product, measured using an evaluation scale and a perceived health risk scale, will be modeled with nicotine delivery and flavor as predictors. For the third aim, a Cigarette/EC Purchase Task will measure behavioral economics of usual brand cigarettes versus EC options. The research proposed in this application is innovative, in the applicant?s opinion, because it examines the combination of physiological, subjective, and behavioral measures of abuse potential manipulating flavor and nicotine dose in the popular EC, JUUL. This proposal is significant because it is expected to provide valuable insight into how nicotine and flavor contribute to EC appeal for young adult smokers. Ultimately, such knowledge has the potential to open new horizons for more effective clinical research focused on switching smokers to ECs.